Several changes in RNA formation, processing, and transport have been described in chemically induced liver tumors and in the liver during the exposure to carcinogens. These modulations of RNA metabolism provide a basis for proposed epigenetic mechanisms altered in carcinogenesis. An enhanced RNA formation and release from the nucleus could provide expression of previously epigenetically suppressed information and thereby could underlie the phenotypic expression of cancer. These series of experiments are designed to expand our understanding of the processes of RNA formation using in vitro analysis of DNA-dependent RNA polymerase, to measure both the mechanisms of RNA transport in vitro and in vivo, and to examine the chemical and functional properties of RNA released. Finally, the role of these alterations in cellular transformation will be sought and the universality of enhanced nuclear RNA release tested. These studies will be carried out using murine myeloma and rat livers and several tissue culture cell livers, isolated DNA-dependent RNA polymerase, several templates including chromatin and homologous DNA, and release of RNA from isolated nuclei will be measured. RNA will be analyzed by centrifugation and electrophoresis, its composition by DNA-RNA hybridization, and its function by in vitro translation.